Search of natural polypeptide molecules that affect the nervous systems
of humans and animals with high selectivity and efficiency is
one of the most important tasks of modern biochemistry and therefore
has practical value to pharmacy, medicine and biotechnology.
This work is devoted to identification and investigation of a new family
of peptide components from Agelena orientalis (Agelenidae) spider
venom designated b/d-agatoxins that modulate the activity of insect
sodium channels. Complete amino acid sequences of all peptides (36–
38 residues) were established by automated Edman degradation. Purified
toxins are characterized by a high degree of similarity with each
other (up to 97%) and with some other toxins such as l-agatoxins,
curtatoxins and d-palutoxins. b/d-Agatoxins were tested on Xenopus
laevis oocytes expressing genes of insect sodium channel proteins
using the two-electrode voltage clamp technique. Application of all
studied compounds at concentrations of ~ 100 nM evoked a modulating
effect on the fruit fly Drosophila melanogaster voltage-gated
sodium channels (DmNav1), i.e. inhibition of inactivation (the socalled
a-effect) and a shift of channel activation voltage dependence
(b-effect). This peculiar ‘double’ effect of polypeptide toxins on
sodium channels can be used for structure and function investigations.
Moreover, b/d-agatoxins are characterized by a high specificity towards channels of insects, being totally ineffective on their mammalian
counterparts. Such selectivity of the peptides provides a basis for
creating new highly effective and safe insecticides.